Although tricomplex pan-RAS (ON) inhibitors, such as RMC-6236, constitute a promising class of therapeutics against RAS-driven cancers, their on-target, off-tumor toxicities challenge the dosing strategy and the safety of drug combinations.
Inactivation of the tumor suppressor p53 occurs in approximately half of human cancer cases. In particular, the Y220C point mutation, which induces p53 misfolding and inactivation, is found in about 1% of solid tumors. Previous research identified a unique, druggable pocket on the p53 surface created by this mutation that constitutes a promising cancer therapeutic target.
In glioblastoma multiforme, MTAP loss leads to MTA accumulation, which partially inhibits PRMT5, making the cells reliant on residual PRMT5 activity for survival. Targeting this remaining PRMT5 with MTA-cooperative inhibitors induces synthetic lethality, representing a promising targeted approach for MTAP-deleted gliomas. Researchers from Ryvu Therapeutics SA reported the preclinical profile of RVU-305, a PRMT5 inhibitor, in MTAP-deleted cancer models.
In preclinical studies at Sunshine Lake Pharma Co. Ltd., researchers investigated the antiviral and immune-modulatory potential of HEC-191834, a novel and highly selective human Toll-like receptor 8 (TLR8) agonist, in chronic hepatitis B virus (HBV) models, as well as its activity when combined with siRNA.
The inhibition of PD-L1 and VEGF individually or in combination has shown efficacy across several solid tumor types, but not all patients respond to therapy or respond for short duration. IMM-2510 is a novel bispecific antibody developed by Immuneonco Biopharmaceuticals Inc. that targets both PD-L1 and VEGF, thus achieving both angiogenesis inhibition and immune checkpoint blockade.
Developing new gene therapies for autosomal dominant polycystic kidney disease (ADPKD) is still a challenge to date. A group of researchers from the Johns Hopkins Medicine in Baltimore has presented results from evaluation of a new gene therapy for treating ADPKD, AAV1-CBdelta27-264CFTR, where they focused on the surface receptors expressed in cystic epithelia.
Researchers from Tango Therapeutics Inc. presented preclinical efficacy data on TNG-260, an inhibitor of the co-repressor of repressor element-1 silencing transcription (CoREST) deacetylase complex, designed to treat immunotherapy-resistant STK11-mutant tumors.
During the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, scientists from Plexium Inc. presented the identification of a new class of potent, selective, cereblon (CRBN)-based molecular glue degraders of CDK2 using its proprietary monovalent degrader platform.
At the recent AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, researchers from Aurigene Oncology Ltd. presented the discovery and clinical characterization of novel macrocyclic KIF18A inhibitors.
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